Clinical imaging of macular holes

The term “macular hole” was first used to describe a partial- or full-thickness hole in the foveolar area. The area is susceptible to degeneration and hole formation because of its extreme thinness, avascularity, and lack of support by the neural and Müller cells.

The firm attachment of the vitreous to the basal lamina in the perifoval area may be important in the pathogenesis of hole formation.¹

The definitions of macular pseudohole (MPH) and lamellar macular hole (LMH) have been the subject of much discussion. A loss of foveal tissue is mandatory for a diagnosis of LMH² (Figure 1).

Pathogenesis

The exact cause of macular hole remains unknown. The first reported macular holes in the late 19th century were believed to result from trauma that caused cystoid changes in the macula.

Concurrent with the discovery around 1970 that the majority of macular holes were not associated with trauma, the predominant thought was that macular hole etiology was related solely to the presence of cystoid macular edema (CME) (Figure 1).³

Macular cysts are most often the result of chronic edema with coalescence of smaller cysts into a single or several larger cysts. Diabetic macular edema (DME) is a common condition associated with macular cysts.

In a study of 90 macular holes, trauma was involved in nine instances. The remaining cases were idiopathic, although ametropia and systemic hypertension were possible factors.⁴

Retinal pigment epithelial hypertrophy and hyperplasia may be seen in the area of both lamellar and complete macular holes. Outer LMHs may be seen with the breakdown of the blood ocular barrier at the retinal pigment epithelium (RPE) level. Retinal glial cells may grow onto the inner surface of the retina at the margin of a lamellar or complete macular hole.

Occasionally, a hole or attenuated area in an epiretinal membrane (ERM) in the macular area may simulate a macular hole (pseudohole).⁵

Diabetes mellitus was the most common condition associated with macular cysts. Residual CME was the most prevalent accompanying pathologic feature.

 Wrinkling of the internal limiting membrane (ILM) and/or vitreous traction with or without an operculum was infrequently associated with macular hole.

Primary macular hole is commonly idiopathic.

Secondary macular hole occurs when the hole is caused by other pathologies not associated with VTM.

The most common non-traumatic entities include:

• CME

• Diabetic macular edema (DME)

• Blunt trauma

• High myopia

• Solar retinopathy

• Severe hypertensive retinopathy

In reality, the etiology of macular hole is probably multifactorial, and determining which is the primary event is less important than the recognition that VTM, foveolar dehiscence, and other factors play a role.

Prior to the advent of optical coherence tomography (OCT) imaging, J. Donald Gass, MD, labeled these as vitreal interface maculopathies. Dr. Gass postulated that macular holes develop not from antero-posterior traction, as commonly thought, but rather from tangential traction that occurs when the posterior vitreous contracts.¹

Clinically, these entities have been described as surface wrinkling retinopathy, cellophane retinopathy, and the more modern ERM.

Epidemiology

Macular holes are most commonly unilateral, although there is an 5 to 15 percent change of macular hole developing in the fellow eye. About 75 percent of the time, they are associated with vitreomacular traction (VTM). They represent about 1.9 percent of visually impaired eyes ranging from 20/40 through 20/200.⁶

They are predominately found (2:1) in the female population with an average age of 6 to 80 years (mean 65). Most macular holes are atraumatic or idiopathic in nature. They tend to enlarge over time and can contribute to epiretinal membrane formation.

Classification of macular hole

Dr. Gass classified macular hole in four stages:⁷

• Stage Ia and 1b: Localized perifoveal PVD, loss of umbo, cystic changes, sometimes foveal yellow spot

• Stage 2: Partial thickness; at this stage, treatment is generally peeling of the hyaloid with gas bubble

• Stage 3: Full thickness; operculum detached

• Stage 4: Completed PVD, hyaloid is no longer attached; a full thickness hole

Stage 1A, 1B

Gass divided the initial stage into Stage 1A, impending macular hole, and Stage 1B, an occult hole. Stage 1A has loss of the foveolar depression with a central yellow spot. Stage 1B appears as a yellow ring that is believed to represent centrifugal displacement of the foveolar retina and xanthophyll.

An “aborted” macular hole has the outer photoreceptor layer intact.

LMHs typically appear as round or irregular-shaped, well-circumscribed reddish lesions on biomicroscopy, but clinical detection at an early stage can be difficult. They usually resolve on their own.

Stage 2

Partial macular hole: Small central or arcuate perifoveal dehiscence. A minute hole forms near the center of the detached fovea. This is not an inevitable process. In 50 percent of cases, the vitreofoveal attachment spontaneously separates before a hole forms. This is followed by restoration of the normal foveal depression and improved visual acuity 20/50 to 20/80. Some 74 percent progress to Stage 3 (Figure 2).

Stage 3

Full-thickness hole with detached operculum: The most common presentation is yellow deposits at the RPE level. The full-thickness hole has a cuff of subretinal fluid >450 µm in size with a detached operculum. No PVD is present, and visual acuity is typically poor: 20/100 to 20/400. At this point, the hole stabilizes or, in the worst-case scenario, progresses slowly. (Figure 3)

Stage 4

The complete or “through-and-through hole: Completed PVD, hyaloid is no longer attached. At this point, a full thickness or loss of foveal tissue deep to the RPE with a loss of its pigment (xanthophylls) is the result. Usually associated with fully resolved VTM. (Figures 4-6)

The VTM theory of macular hole pathogenesis gained in popularity with the recognition that peripheral retinal breaks occur secondary to vitreoretinal traction on the posterior vitreous hyaloid and that strong adhesion exists between the vitreous and fovea. (Figure 7)

Pseudomacular hole

A pseudohole is when spontaneous partial detachment of the membrane has occurred inferiorly with a crescent-shaped scroll at the membrane edge. This makes it appear as if the fovea has a hole. OCT reveals an attached preretinal membrane that pulls the inner parts of the fovea toward the center, simulating a macular hole with cystoid changes in the central retina.

Myopia and macular hole

Malignant myopia and macular holes can be associated with high myopia and are referred to as myopic macular holes. High myopia is defined as a refractive error ≥−6.00 D of axial myopia with an axial length of >26 mm.⁸

The already-thin foveal tissue becomes even thinner with stretching of the retina, leading to development of the macular hole. (Figures 8A-C)

Traumatic macular hole

Formation of a traumatic macular hole is believed to be related to rapid changes at the vitreofoveal interface that occur during the traumatic event.

In contrast to idiopathic macular holes that may occur over the course of weeks to months, the formation of traumatic macular holes happens more quickly.⁷

Other associated findings seen in traumatic macular holes-not present in idiopathic macular holes-include retinal pigment epithelium (RPE) mottling with damage to the RPE. Damage to the RPE appears to be directly related to the trauma. Despite the presence of RPE damage, visual recovery is still possible.^9,10

Fortunately, the surgical closure rate (96 percent) and the visual improvement in traumatic macular holes are similar to that found with idiopathic macular hole closures.¹⁰ (Figures 9A and B)

Early macular hole imaging

From the 1970s through the early 1990s, color fundus photography and/or imaging utilizing the red-free filters built into fundus camera for angiography was the only modality available. Diagnostic B-scan echography still remains a poor modality of imaging for macular hole given its low resolution (about 150 μm) and the inability for sound to “see” the typical 5-μm hole.

Fluorescein angiography (FA) also remains a poor option for imaging due to its low resolution and lack of hemodynamic properties to macular hole. Typically, angiography might disclose hyperfluorescence in the early frames, with no leak in late frames (window defect).

However, FA is invasive and carries potential risks for adverse reactions. Optical coherence tomography (OCT) and fundus autofluorescence (FAF) images have now replaced FA in the evaluation of patients with all stages of macular hole.

Role of OCT

OCT is able to noninvasively detect the presence of macular hole and changes in the surrounding retina. At an average of 3- to 5-μm resolution, minute changes can be detected.

The VTM theory of macular hole pathogenesis gained in popularity with the recognition that peripheral retinal breaks occur secondary to vitreoretinal traction and that strong adhesion exists between the vitreous and fovea.¹⁰

OCT has enhanced our understanding of the orientation of this traction, which is now thought to be predominantly anteroposterior (AP) in direction.

OCT can also be used to determine early macular hole closure following surgery. However, it may be difficult to obtain good quality images because of the presence of gas in the eye, particularly if the eye is already pseudophakic.

Role of fundus autofluorescence

One of the first studies published on the usefulness of FAF in patients with macular holes compared FAF with corresponding color fundus photographs, FA of the affected eye, and FAF images of the unaffected, contralateral eye.¹¹

An increased signal at the sight of the hole by FAF was validated. In FAF, the signal derives predominantly from the lipofuscin in the RPE. In the normal eye, this signal is attenuated at the center of the macula by the presence of the luteal pigment, which has a higher concentration along the outer plexiform layer at the fovea.¹²

In the case of macular hole, and subsequent loss of luteal pigment overlying the defect, a marked FAF signal can be observed, delineating the hole.

In vivo imaging of the FAF can be performed with commercially available adapted fundus cameras or confocal scanning laser ophthalmoscopes (cSLO). The cSLO needs specialized filters with an excitation wavelength of approximately 488 to 580 nm and a barrier filter at 500 to 715 nm, depending on the instrument used.

While FAF has replaced FA in the evaluation of macular hole, it cannot replace OCT in all cases. OCT may still be needed when the differentiation between a lamellar hole (FAF will demonstrated increased foveal AF or FAF positive) and a pseudohole (FAF will show a normal pattern [FAF negative]).

Tips for imaging macular hole

Use the highest-resolution cube or line scan over the foveal area to capture the precise scan that best demonstrates evidence of a hole. Shorten the scan line to about 10° to maximize imaging only in the area necessary. Double-check the segmentation lines for accuracy in metrics.
(Figures 10A, B)

If your OCT has an en face feature, add this to maximize imaging of the fluid cuff. VMT often results in intraretinal splitting along a plane of anatomical weakness at Henle’s Fiber Layer and the outer plexiform layer, resulting in a characteristic en face appearance. The ability to visualize and quantify the extent of intraretinal splitting with a single en face image provides a useful tool for monitoring disease progression.

Future macular hole imaging

With the advent of optical coherence tomography angiography (OCTA), this new modality may hold the key to the best of both imaging worlds-angiography and OCT.

References

1. Gass, JDM. Stereoscopic atlas of macular diseases: diagnosis and treatment. 2nd edition. Mosby; 1977:334.

2. Haochine B, Massin P, Tadayoni R, Erginay A, Gaudric A. Diagnosis of macular pseudoholes and lamellar macular hole by optical coherence tomography. Am J Ophthalmol. 2004 Nov;138(5):732-9.

3. Aaberg TM, Blair CJ, Gass JD. Macular holes. Am J Ophthalmol. 1970 Apr;69(4):555-62.

4. Spencer William H. Ophthalmic Pathology: An Atlas and Textbook. Vitreous and Retina. Volume 2. W.B. Saunders; 1985;991.

5. Frangieh GT, Green WR, Engel HM. A histopathologic study of macular cysts and holes. Retina. 1981;1(4):311-36.

6. Mehdizadeh M, Jamshidian M, Nowroozzadeh MH. Macular hole epidemiology. Ophthalmology. 2010 Dec;117(12):2442-3.

7. Johnson RN, McDonald HR, Lewis H, et al. Traumatic macular hole: observations, pathogenesis, and results of vitrectomy surgery. Ophthalmology. 2001 May;108(5):853-7.

8. Wu TT, Kung YH. Comparison of anatomical and visual outcomes of macular hole surgery in patients with high myopia vs. non-high myopia: a case-control study using optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2012 Mar;250(3):327-31.

9. Chow DR, Williams GA, Trese MT, Margherio RR, Ruby AJ, Ferrone PJ. Successful closure of traumatic macular holes. Retina. 1999;19(5):405-9.

10. Dayani PN1, Maldonado R, Farsiu S, Toth CA. Intraoperative use of handheld spectral domain optical coherence tomography imaging in macular surgery. Retina. 2009 Nov-Dec;29(10):1457-68.

11.von Rückmann A, Fitzke FW, Gregor ZJ. Fundus autofluoresence in patients with macular holes imaged with a laser scanning ophthalmoscope. Br J Ophthalmol. 1998 Apr;82(4):346-51.

12. McBain VA, Forrester JV, Lois N. Fundus autofluorescence in the diagnosis of cystoid macular oedema. Br J Ophthalmol. 2008 Jul;92(7):946-9.